Combination of Cadonilimab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-006)

NCT06143748 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: B2023-425
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer. However, as high as more than 40% of patients with esophageal cancer experienced locoregional recurrence after definitive CRT. Immune checkpoint inhibitors targeting PD-1/PD-L1 and/or CTLA-4 have shown substantial clinical benefits in advanced esophageal cancer. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in esophageal cancer. The aim of this study was to evaluate the efficacy and safety of cadonilimab (a bispecific PD-1/CTLA-4 antibody) combined with induction chemotherapy followed by definitive radiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Conditions

Esophagus Cancer

Keywords

Esophageal squamous cell carcinoma; Radiotherapy; Cadonilimab; Induction chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Three-year follow-up from the date of enrollment to the date of disease progression or last follow-up

  From date of enrollment until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 36 months.

Secondary Outcomes (4)

• Overall survival

  From date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 36 months.

• Clinical complete response

  3 months after radiotherapy (plus or minus 7 days)

• Duration of response

  From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 36 months.

• Treatment-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Other Outcomes (3)

• Correlation between immune signature and survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

• Correlation between dynamic change of ctDNA and survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

• Correlation between genetic biomarkers and survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Study Arms (1)

The study group

EXPERIMENTAL

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135 mg/m2, cisplatin 75 mg/m2, and cadonilimab 10 mg/kg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with 2 cycles of cadonilimab. After the completion of radiotherapy, patients will then receive 12 additional cycles of cadonilimab.

Drug: Cadonilimab; Drug: Paclitaxel and cisplatin; Radiation: intensity-modulated radiotherapy

Interventions

Cadonilimab DRUG

Patients received cadonilimab 10 mg/kg every 3 weeks for up to 16 cycles.

Also known as: AK104

The study group

Paclitaxel and cisplatin DRUG

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will not receive chemotherapy during radiotherapy.

Also known as: taxol, DDP

The study group

intensity-modulated radiotherapy RADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Also known as: IMRT

The study group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous cell carcinoma of the esophagus;
• Locally advanced, and absence of distant metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan, stage II-IVA (according to UICC TNM version 8);
• Not suitable for surgery (either for medical reasons or patient's choice);
• Age at diagnosis 18 to 75 years;
• No prior cancer therapy;
• Estimated life expectancy \>6 months;
• Eastern Cooperative Oncology Group performance status ≤ 2
• No history of concomitant or previous malignancy;
• The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate \>60 mL/min;
• Ability to understand the study and sign informed consent.

You may not qualify if:

• Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
• Patients with distant metastasis disease or esophageal fistula at diagnosis;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
• Patients who have a preexisting or coexisting bleeding disorder;
• Female patients who are pregnant or lactating;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• Presence of CTC grade ≥2 peripheral neuropathy;
• A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
• Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
• A history of interstitial lung disease or non-infectious pneumonia;
• A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

Related Publications (4)

• Gao X, Xu N, Li Z, Shen L, Ji K, Zheng Z, Liu D, Lou H, Bai L, Liu T, Li Y, Li Y, Fan Q, Feng M, Zhong H, Huang Y, Lou G, Wang J, Lin X, Chen Y, An R, Li C, Zhou Q, Huang X, Guo Z, Wang S, Li G, Fei J, Zhu L, Zhu H, Li X, Li F, Liao S, Min Q, Tang L, Shan F, Gong J, Gao Y, Zhou J, Lu Z, Li X, Li J, Ren H, Liu X, Yang H, Li W, Song W, Wang ZM, Li B, Xia M, Wu X, Ji J. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Lancet Oncol. 2023 Oct;24(10):1134-1146. doi: 10.1016/S1470-2045(23)00411-4.

  PMID: 37797632 RESULT

• Frentzas S, Gan HK, Cosman R, Coward J, Tran B, Millward M, Zhou Y, Wang W, Xia D, Wang ZM, Li B, Xia M, Desai J. A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors. Cell Rep Med. 2023 Nov 21;4(11):101242. doi: 10.1016/j.xcrm.2023.101242. Epub 2023 Oct 17.

  PMID: 37852261 RESULT

• Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380.

  PMID: 35108470 RESULT

• Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.

  PMID: 36990609 RESULT

MeSH Terms

Conditions

Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma

Interventions

TP protocol; Paclitaxel; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Mian Xi, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: November 22, 2023
• Study Start: March 2, 2024
• Primary Completion (Estimated): June 10, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)